UBAP1

UniProt ID: Q9NZ09
Organism: Homo sapiens
Review Status: COMPLETE
📝 Provide Detailed Feedback

Gene Description

UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. Its core functions are ubiquitin binding through UBA/SOUBA domains, recognition/sorting of ubiquitinated endosomal cargo into multivesicular bodies, and endosome-specific ESCRT-I complex membership. General ESCRT-I membrane-fission annotations from MVB12A/VPS37B structural work should not be treated as direct UBAP1 evidence.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000813 ESCRT I complex
IBA
GO_REF:0000033 		ACCEPT
Summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation.
Reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Component of the ESCRT-I complex
file:human/UBAP1/UBAP1-uniprot.txt
consists of TSG101, VPS28, VPS37A and UBAP1
PMID:21757351
identify a novel ESCRT-I component
PMID:21757351
defines an endosome-specific ESCRT-I complex
PMID:22405001
coassembles in a stable 1:1:1:1 complex
GO:0043130 ubiquitin binding
IBA
GO_REF:0000033 		ACCEPT
Summary: Ubiquitin binding is a core UBAP1 molecular-function annotation.
Reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/UBAP1/UBAP1-uniprot.txt
Interacts (via UBA domains) with ubiquitinated proteins
PMID:21757351
endosomal ubiquitin homeostasis
PMID:22405001
solenoid of overlapping UBAs
PMID:22405001
interact with ubiquitin
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
IBA
GO_REF:0000033 		ACCEPT
Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process.
Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
sorting of endocytic ubiquitinated cargos
PMID:21757351
required for sorting EGFR to the MVB
PMID:21757351
endosomal ubiquitin homeostasis
PMID:22405001
essential for degradation of antiviral cell-surface proteins
GO:0000813 ESCRT I complex
IEA
GO_REF:0000002 		ACCEPT
Summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation.
Reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Component of the ESCRT-I complex
file:human/UBAP1/UBAP1-uniprot.txt
consists of TSG101, VPS28, VPS37A and UBAP1
PMID:21757351
identify a novel ESCRT-I component
PMID:21757351
defines an endosome-specific ESCRT-I complex
PMID:22405001
coassembles in a stable 1:1:1:1 complex
GO:0005768 endosome
IEA
GO_REF:0000044 		ACCEPT
Summary: endosome localization is supported and relevant to UBAP1/ESCRT-I function.
Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Endosome
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Recruited to endosomes as part of the ESCRT-I complex
PMID:21757351
endosome-specific ESCRT-I complex
GO:0005829 cytosol
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: cytosol is supported as a localization context but is not the core functional site.
Reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Cytoplasm, cytosol
GO:0043130 ubiquitin binding
IEA
GO_REF:0000002 		ACCEPT
Summary: Ubiquitin binding is a core UBAP1 molecular-function annotation.
Reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/UBAP1/UBAP1-uniprot.txt
Interacts (via UBA domains) with ubiquitinated proteins
PMID:21757351
endosomal ubiquitin homeostasis
PMID:22405001
solenoid of overlapping UBAs
PMID:22405001
interact with ubiquitin
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
IEA
GO_REF:0000002 		ACCEPT
Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process.
Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
sorting of endocytic ubiquitinated cargos
PMID:21757351
required for sorting EGFR to the MVB
PMID:21757351
endosomal ubiquitin homeostasis
PMID:22405001
essential for degradation of antiviral cell-surface proteins
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		MARK AS OVER ANNOTATED
Summary: Protein binding is too generic to represent UBAP1 function.
Reason: The informative molecular function is ubiquitin binding, and the informative component/process terms are ESCRT-I complex and MVB sorting.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/UBAP1/UBAP1-uniprot.txt
Interacts (via UBA domains) with ubiquitinated proteins
PMID:21757351
endosomal ubiquitin homeostasis
PMID:22405001
solenoid of overlapping UBAs
PMID:22405001
interact with ubiquitin
file:human/UBAP1/UBAP1-uniprot.txt
Component of the ESCRT-I complex
file:human/UBAP1/UBAP1-uniprot.txt
consists of TSG101, VPS28, VPS37A and UBAP1
PMID:21757351
identify a novel ESCRT-I component
PMID:21757351
defines an endosome-specific ESCRT-I complex
PMID:22405001
coassembles in a stable 1:1:1:1 complex
GO:0005829 cytosol
IDA
GO_REF:0000052 		KEEP AS NON CORE
Summary: cytosol is supported as a localization context but is not the core functional site.
Reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Cytoplasm, cytosol
GO:0000813 ESCRT I complex
IPI
PMID:21757351
UBAP1 is a component of an endosome-specific ESCRT-I complex... 		ACCEPT
Summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation.
Reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Component of the ESCRT-I complex
file:human/UBAP1/UBAP1-uniprot.txt
consists of TSG101, VPS28, VPS37A and UBAP1
PMID:21757351
identify a novel ESCRT-I component
PMID:21757351
defines an endosome-specific ESCRT-I complex
PMID:22405001
coassembles in a stable 1:1:1:1 complex
GO:0010008 endosome membrane
NAS
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topolo... 		ACCEPT
Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Endosome
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Recruited to endosomes as part of the ESCRT-I complex
PMID:21757351
endosome-specific ESCRT-I complex
GO:0036258 multivesicular body assembly
NAS
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topolo... 		ACCEPT
Summary: multivesicular body assembly is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process.
Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
sorting of endocytic ubiquitinated cargos
PMID:21757351
required for sorting EGFR to the MVB
PMID:21757351
endosomal ubiquitin homeostasis
PMID:22405001
essential for degradation of antiviral cell-surface proteins
GO:0043328 protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
NAS
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topolo... 		ACCEPT
Summary: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process.
Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
sorting of endocytic ubiquitinated cargos
PMID:21757351
required for sorting EGFR to the MVB
PMID:21757351
endosomal ubiquitin homeostasis
PMID:22405001
essential for degradation of antiviral cell-surface proteins
GO:0090148 membrane fission
NAS
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topolo... 		MARK AS OVER ANNOTATED
Summary: Membrane fission is over-transferred for UBAP1 as written.
Reason: The cited structural/autophagy work uses a VPS37B-MVB12A-containing ESCRT-I headpiece and VPS28 mutants, not UBAP1-containing ESCRT-I.
Supporting Evidence:
PMID:32424346
comprising TSG101-VPS28-VPS37B-MVB12A
PMID:32424346
Mutation of VPS28 helical interface residues
file:human/UBAP1/UBAP1-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/UBAP1/UBAP1-uniprot.txt
Interacts (via UBA domains) with ubiquitinated proteins
GO:0005768 endosome
EXP
PMID:21757351
UBAP1 is a component of an endosome-specific ESCRT-I complex... 		ACCEPT
Summary: endosome localization is supported and relevant to UBAP1/ESCRT-I function.
Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Endosome
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Recruited to endosomes as part of the ESCRT-I complex
PMID:21757351
endosome-specific ESCRT-I complex
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-184269 		ACCEPT
Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Endosome
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Recruited to endosomes as part of the ESCRT-I complex
PMID:21757351
endosome-specific ESCRT-I complex
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-3149434 		ACCEPT
Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Endosome
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Recruited to endosomes as part of the ESCRT-I complex
PMID:21757351
endosome-specific ESCRT-I complex
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-3159232 		ACCEPT
Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Endosome
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Recruited to endosomes as part of the ESCRT-I complex
PMID:21757351
endosome-specific ESCRT-I complex
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-917696 		ACCEPT
Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Endosome
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Recruited to endosomes as part of the ESCRT-I complex
PMID:21757351
endosome-specific ESCRT-I complex
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-917730 		ACCEPT
Summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
Reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Endosome
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Recruited to endosomes as part of the ESCRT-I complex
PMID:21757351
endosome-specific ESCRT-I complex
GO:0000813 ESCRT I complex
IDA
PMID:21757351
UBAP1 is a component of an endosome-specific ESCRT-I complex... 		ACCEPT
Summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation.
Reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Component of the ESCRT-I complex
file:human/UBAP1/UBAP1-uniprot.txt
consists of TSG101, VPS28, VPS37A and UBAP1
PMID:21757351
identify a novel ESCRT-I component
PMID:21757351
defines an endosome-specific ESCRT-I complex
PMID:22405001
coassembles in a stable 1:1:1:1 complex
GO:0005829 cytosol
IDA
PMID:21757351
UBAP1 is a component of an endosome-specific ESCRT-I complex... 		KEEP AS NON CORE
Summary: cytosol is supported as a localization context but is not the core functional site.
Reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Cytoplasm, cytosol
GO:0043130 ubiquitin binding
IDA
PMID:21757351
UBAP1 is a component of an endosome-specific ESCRT-I complex... 		ACCEPT
Summary: Ubiquitin binding is a core UBAP1 molecular-function annotation.
Reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/UBAP1/UBAP1-uniprot.txt
Interacts (via UBA domains) with ubiquitinated proteins
PMID:21757351
endosomal ubiquitin homeostasis
PMID:22405001
solenoid of overlapping UBAs
PMID:22405001
interact with ubiquitin
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
IMP
PMID:21757351
UBAP1 is a component of an endosome-specific ESCRT-I complex... 		ACCEPT
Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process.
Reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
sorting of endocytic ubiquitinated cargos
PMID:21757351
required for sorting EGFR to the MVB
PMID:21757351
endosomal ubiquitin homeostasis
PMID:22405001
essential for degradation of antiviral cell-surface proteins
GO:0005737 cytoplasm
IDA
GO_REF:0000054 		KEEP AS NON CORE
Summary: cytoplasm is supported as a localization context but is not the core functional site.
Reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting.
Supporting Evidence:
file:human/UBAP1/UBAP1-uniprot.txt
Predominantly cytosolic
file:human/UBAP1/UBAP1-uniprot.txt
Cytoplasm, cytosol

Core Functions

UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant that organizes a TSG101-VPS28-VPS37A-UBAP1 complex for ubiquitinated cargo sorting.

Molecular Function:
ubiquitin binding
Directly Involved In:
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway multivesicular body assembly
Cellular Locations:
endosome endosome membrane
In Complex:
ESCRT I complex
Supporting Evidence:
  • file:human/UBAP1/UBAP1-uniprot.txt
    Component of the ESCRT-I complex
  • file:human/UBAP1/UBAP1-uniprot.txt
    consists of TSG101, VPS28, VPS37A and UBAP1
  • PMID:21757351
    identify a novel ESCRT-I component
  • PMID:21757351
    defines an endosome-specific ESCRT-I complex
  • PMID:22405001
    coassembles in a stable 1:1:1:1 complex
  • file:human/UBAP1/UBAP1-uniprot.txt
    Binds to ubiquitinated cargo proteins
  • file:human/UBAP1/UBAP1-uniprot.txt
    Interacts (via UBA domains) with ubiquitinated proteins
  • PMID:21757351
    endosomal ubiquitin homeostasis
  • PMID:22405001
    solenoid of overlapping UBAs
  • PMID:22405001
    interact with ubiquitin
  • file:human/UBAP1/UBAP1-uniprot.txt
    sorting of endocytic ubiquitinated cargos
  • PMID:21757351
    required for sorting EGFR to the MVB
  • PMID:21757351
    endosomal ubiquitin homeostasis
  • PMID:22405001
    essential for degradation of antiviral cell-surface proteins
  • file:human/UBAP1/UBAP1-uniprot.txt
    Endosome
  • file:human/UBAP1/UBAP1-uniprot.txt
    Predominantly cytosolic
  • file:human/UBAP1/UBAP1-uniprot.txt
    Recruited to endosomes as part of the ESCRT-I complex
  • PMID:21757351
    endosome-specific ESCRT-I complex

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000054
Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
PMID:21757351
UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.
Reactome:R-HSA-184269
Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by the ESCRT-I complex
Reactome:R-HSA-3149434
Transport of GAG to the Plasma Membrane
Reactome:R-HSA-3159232
Recruitment Of HIV Virion Budding Machinery
Reactome:R-HSA-917696
Cargo Sequestration
Reactome:R-HSA-917730
Cargo Recognition And Sorting
PMID:22405001
The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain.
file:human/UBAP1/UBAP1-uniprot.txt
UniProtKB record for human UBAP1
file:human/UBAP1/UBAP1-notes.md
UBAP1 review notes

Suggested Questions for Experts

Q: Should UBAP1 membrane-fission annotations be removed or kept non-core unless UBAP1-containing ESCRT-I is directly tested in membrane-scission/autophagosome-closure assays?

Suggested experts: GO ESCRT curators, GO autophagy editors

Q: Should generic UBAP1 protein-binding annotations be replaced by ubiquitin binding and ESCRT-I complex membership?

Suggested experts: GO molecular function editors, UniProt curators

Suggested Experiments

Experiment: Compare purified or reconstituted UBAP1-ESCRT-I and MVB12A-ESCRT-I complexes in membrane-remodeling assays and in cell-based autophagosome-closure assays.

Hypothesis: UBAP1-containing ESCRT-I specializes in endosomal ubiquitinated cargo sorting and should not be assumed to provide the same membrane-fission function as MVB12A-containing ESCRT-I without direct evidence.

Type: UBAP1-containing ESCRT-I membrane remodeling assay

Experiment: Rescue UBAP1 knockout cells with wild-type and SOUBA/UBA mutants and measure EGFR/BST2 cargo degradation, endosomal ubiquitin homeostasis, and ESCRT-I recruitment.

Hypothesis: UBAP1 SOUBA/UBA-mediated ubiquitin binding is required for endosomal cargo sorting.

Type: UBAP1 ubiquitin-binding rescue

📚 Additional Documentation

Notes

(UBAP1-notes.md)

UBAP1 review notes

Scope

UBAP1 is reviewed in the PN ESCRT-I branch. PN entries without PMIDs were used as context only. UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant with direct evidence for ubiquitinated cargo sorting, ubiquitin binding through SOUBA/UBA domains, and endosome localization. It should not inherit MVB12A/VPS37B-specific structural membrane-fission or autophagosome-closure evidence as a core UBAP1 function without UBAP1-specific perturbation data.

Evidence synthesis

UniProt describes UBAP1 as a "Component of the ESCRT-I complex" and states that it "Binds to ubiquitinated cargo proteins" and is required for sorting endocytic ubiquitinated cargo into MVBs [file:human/UBAP1/UBAP1-uniprot.txt, "Component of the ESCRT-I complex"; file:human/UBAP1/UBAP1-uniprot.txt, "Binds to ubiquitinated cargo proteins"; file:human/UBAP1/UBAP1-uniprot.txt, "sorting of endocytic ubiquitinated cargos"]. UniProt also states that UBAP1-containing ESCRT-I consists of TSG101, VPS28, VPS37A, and UBAP1, and that UBAP1 interacts with PTPN23 and ubiquitinated proteins [file:human/UBAP1/UBAP1-uniprot.txt, "consists of TSG101, VPS28, VPS37A and UBAP1"; file:human/UBAP1/UBAP1-uniprot.txt, "Interacts with PTPN23"; file:human/UBAP1/UBAP1-uniprot.txt, "Interacts (via UBA domains) with ubiquitinated proteins"].

The main UBAP1 functional paper defines UBAP1 as an endosome-specific ESCRT-I component. Its abstract reports that mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B, identifies UBAP1 as a novel ESCRT-I component, and says UBAP1 binds HD-PTP/PTPN23 [PMID:21757351, "Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B"; PMID:21757351, "identify a novel ESCRT-I component"; PMID:21757351, "UBAP1 binds the endosomal Bro1 protein"]. It also reports that UBAP1 is required for EGFR sorting to the MVB and endosomal ubiquitin homeostasis, but not cytokinesis, and that UBAP1 plus VPS37A defines an endosome-specific ESCRT-I complex [PMID:21757351, "required for sorting EGFR to the MVB"; PMID:21757351, "endosomal ubiquitin homeostasis"; PMID:21757351, "defines an endosome-specific ESCRT-I complex"]. These support accepting ESCRT-I complex, endosome/endosome membrane, ubiquitin binding, and ubiquitin-dependent MVB sorting.

The UBAP1/SOUBA structural paper directly supports ubiquitin binding and the ESCRT-I complex role. PMID:22405001 reports that UBAP1 coassembles in a stable complex with Vps23/TSG101, VPS28, and VPS37, that its SOUBA domain contains overlapping UBAs, and that those UBAs interact with ubiquitin [PMID:22405001, "coassembles in a stable 1:1:1:1 complex"; PMID:22405001, "solenoid of overlapping UBAs"; PMID:22405001, "interact with ubiquitin"]. It also shows UBAP1-containing ESCRT-I is needed for degradation of antiviral cell-surface proteins, giving a direct cargo-sorting context [PMID:22405001, "essential for degradation of antiviral cell-surface proteins"].

The ComplexPortal/NAS rows that cite PMID:32424346 should be handled carefully. That paper determined a human ESCRT-I headpiece "comprising TSG101-VPS28-VPS37B-MVB12A" and tested VPS28 helical-interface mutants [PMID:32424346, "comprising TSG101-VPS28-VPS37B-MVB12A"; PMID:32424346, "Mutation of VPS28 helical interface residues"]. It supports general ESCRT-I membrane remodeling and can provide background for ESCRT-I context, but it is not direct UBAP1 evidence. Therefore endosome/MVB sorting rows can be retained using UBAP1-specific evidence, while the membrane fission row should be marked over-transferred for UBAP1.

Generic protein binding is not informative for UBAP1. The meaningful molecular functions and components are ubiquitin binding, ESCRT-I complex membership, and endosome-specific cargo sorting. Cytosol/cytoplasm rows are supported as localization context because UBAP1 is predominantly cytosolic and recruited to endosomes, but the core functional site is endosomal ESCRT-I.

Falcon

Falcon deep research was started for UBAP1 on 2026-06-02 but timed out after 600 seconds and did not produce a usable UBAP1-deep-research-falcon.md report. The review therefore relies on the local UniProt, GOA, cached-publication, Reactome, and PN-context evidence summarized above.

Pn Notes

(UBAP1-pn-notes.md)

UBAP1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9NZ09
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-pr-1217 (PR 1217)
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. Its core functions are ubiquitin binding through UBA/SOUBA domains, recognition/sorting of ubiquitinated endosomal cargo into multivesicular bodies, and endosome-specific ESCRT-I complex membership. General ESCRT-I membrane-fission annotations from MVB12A/VPS37B structural work should not be treated as direct UBAP1 evidence.
  • Existing/core annotation action counts: ACCEPT: 20; KEEP_AS_NON_CORE: 4; MARK_AS_OVER_ANNOTATED: 2

PN Consistency Summary

  • Consistency: Deep research (notes), review YAML, and PN annotation agree that UBAP1 is the endosome-specific fourth ESCRT-I subunit (TSG101-VPS28-VPS37A-UBAP1) doing ubiquitin binding + MVB cargo sorting. One internal tension: the PN places UBAP1 under autophagophore-sealing, but the review deliberately argues the autophagy/membrane-fission evidence (PMID:32424346) used VPS37B-MVB12A ESCRT-I, not UBAP1, and so MARK_AS_OVER_ANNOTATED membrane fission. Defensible and well-sourced.
  • PN story / NEW pressure: ESCRT-I membership (GO:0000813), ubiquitin binding (GO:0043130), and MVB catabolism (GO:0043162) are all already captured. The PN-projected GO:0000045 autophagosome assembly is new_to_goa but the review does NOT add it for UBAP1 (no UBAP1-specific phagophore-closure evidence). Verdict: already captured for the endosomal role; autophagosome-assembly over-reaches for UBAP1.
  • Evidence alignment: PN cites only PMID:32424346 (the membrane-scission structure paper). Review's core ESCRT-I evidence is PMID:21757351 (UBAP1 endosome-specific ESCRT-I) + PMID:22405001 (SOUBA), and it treats PMID:32424346 as the over-annotation source — direct divergence in how the shared paper is used.
  • Verdict: Internally consistent and defensible; flag that the PN autophagosome-sealing placement / GO:0000045 projection is not supported by UBAP1-specific evidence (review correctly withholds it).

Full Consistency Review

  • UniProt: Q9NZ09 · batch: proteostasis-pr-1217 · review status: COMPLETE
  • PN placement: ALP …|Sealing of autophagophore membrane|ESCRT-I complex component + UPS …|trafficking|ESCRT-I complex|UBA (UBAP1) ; PN-node mapping: leaf mapped/ok_for_propagation GO:0000813 ESCRT I complex; group mapped GO:0000045 autophagosome assembly; UPS nodes no_mapping/context_only.
  • Consistency: Deep research (notes), review YAML, and PN annotation agree that UBAP1 is the endosome-specific fourth ESCRT-I subunit (TSG101-VPS28-VPS37A-UBAP1) doing ubiquitin binding + MVB cargo sorting. One internal tension: the PN places UBAP1 under autophagophore-sealing, but the review deliberately argues the autophagy/membrane-fission evidence (PMID:32424346) used VPS37B-MVB12A ESCRT-I, not UBAP1, and so MARK_AS_OVER_ANNOTATED membrane fission. Defensible and well-sourced.
  • PN story / NEW pressure: ESCRT-I membership (GO:0000813), ubiquitin binding (GO:0043130), and MVB catabolism (GO:0043162) are all already captured. The PN-projected GO:0000045 autophagosome assembly is new_to_goa but the review does NOT add it for UBAP1 (no UBAP1-specific phagophore-closure evidence). Verdict: already captured for the endosomal role; autophagosome-assembly over-reaches for UBAP1.
  • Mapping strategy: UBAP1 does not justify the ALP group's GO:0000045 projection — the review's evidence argument is that autophagic ESCRT-I uses MVB12A/VPS37B not UBAP1. PN-projected GO:0000045 is therefore broader/mis-attributed for this gene (TOMM20/HSPA8-style over-reach). GO:0000813 leaf mapping is correct.
  • Evidence alignment: PN cites only PMID:32424346 (the membrane-scission structure paper). Review's core ESCRT-I evidence is PMID:21757351 (UBAP1 endosome-specific ESCRT-I) + PMID:22405001 (SOUBA), and it treats PMID:32424346 as the over-annotation source — direct divergence in how the shared paper is used.
  • Verdict: Internally consistent and defensible; flag that the PN autophagosome-sealing placement / GO:0000045 projection is not supported by UBAP1-specific evidence (review correctly withholds it).

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/UBAP1/UBAP1-ai-review.yaml
  • PN workbook rows: 2

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-I complex component

  • UniProt: Q9NZ09
  • In branches: ALP, UPS
  • Notes: Component of the ESCRT-I complex, involved in autophagosome closure
  • PN references (titles):
    • A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission | Nature Structural & Molecular Biology
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0000813 ESCRT I complex]
      rationale: This leaf is restricted to ESCRT-I components used in autophagophore sealing. The shared GO assertion is ESCRT I complex membership.
    • [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
      rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
    • [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
      status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
      rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 2: Ubiquitin Proteasome System | Ubiquitin and UBL binding | trafficking | ESCRT-I complex | UBA (UBAP1)

  • UniProt: Q9NZ09
  • In branches: ALP, UPS
  • Signature domains: IPR049467, IPR015940
  • Auxiliary domains: (none)
  • PN-node mapping records (path + ancestors):
    • [subtype] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|ESCRT-I complex|UBA (UBAP1)
      status=no_mapping scope= GO=[]
      rationale: Reviewed manually as a UPS source node. No single GO term is appropriate for direct propagation from this PN label without narrower context or gene-level evidence.
    • [type] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|ESCRT-I complex
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
    • [group] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
    • [class] Ubiquitin Proteasome System|Ubiquitin and UBL binding
      status=context_only scope=too_broad_to_propagate GO=[GO:0140036 ubiquitin-modified protein reader activity]
      rationale: This class records ubiquitin/UBL-reader context, but the subtree mixes ubiquitin, SUMO, UBL-domain, domain-architecture, catalytic, signaling, trafficking, and nucleic-acid process buckets. It is useful context, not a safe direct propagation.
    • [branch] Ubiquitin Proteasome System
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

Projected GO annotations (2)

  • GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
  • GO:0000813 ESCRT I complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: Q9NZ09
gene_symbol: UBAP1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. Its core
  functions are ubiquitin binding through UBA/SOUBA domains, recognition/sorting of ubiquitinated endosomal cargo into multivesicular
  bodies, and endosome-specific ESCRT-I complex membership. General ESCRT-I membrane-fission annotations from MVB12A/VPS37B
  structural work should not be treated as direct UBAP1 evidence.
alternative_products:
- name: '1'
  id: Q9NZ09-1
- name: '2'
  id: Q9NZ09-2
  sequence_note: VSP_013650
- name: '3'
  id: Q9NZ09-3
  sequence_note: VSP_046866
- name: '4'
  id: Q9NZ09-4
  sequence_note: VSP_046867
existing_annotations:
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation.
    action: ACCEPT
    reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes.
    additional_reference_ids: &id001
    - PMID:21757351
    - PMID:22405001
    - file:human/UBAP1/UBAP1-uniprot.txt
    - file:human/UBAP1/UBAP1-notes.md
    supported_by: &id002
    - &id012
      reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: Component of the ESCRT-I complex
    - &id013
      reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: consists of TSG101, VPS28, VPS37A and UBAP1
    - &id014
      reference_id: PMID:21757351
      supporting_text: identify a novel ESCRT-I component
    - &id015
      reference_id: PMID:21757351
      supporting_text: defines an endosome-specific ESCRT-I complex
    - &id016
      reference_id: PMID:22405001
      supporting_text: coassembles in a stable 1:1:1:1 complex
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Ubiquitin binding is a core UBAP1 molecular-function annotation.
    action: ACCEPT
    reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis.
    additional_reference_ids: &id003
    - PMID:21757351
    - PMID:22405001
    - file:human/UBAP1/UBAP1-uniprot.txt
    - file:human/UBAP1/UBAP1-notes.md
    supported_by: &id004
    - &id007
      reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: Binds to ubiquitinated cargo proteins
    - &id008
      reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: Interacts (via UBA domains) with ubiquitinated proteins
    - &id009
      reference_id: PMID:21757351
      supporting_text: endosomal ubiquitin homeostasis
    - &id010
      reference_id: PMID:22405001
      supporting_text: solenoid of overlapping UBAs
    - &id011
      reference_id: PMID:22405001
      supporting_text: interact with ubiquitin
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core
      UBAP1/ESCRT-I endosomal cargo-sorting process.
    action: ACCEPT
    reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
    additional_reference_ids: &id005
    - PMID:21757351
    - PMID:22405001
    - file:human/UBAP1/UBAP1-uniprot.txt
    - file:human/UBAP1/UBAP1-notes.md
    supported_by: &id006
    - &id021
      reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: sorting of endocytic ubiquitinated cargos
    - &id022
      reference_id: PMID:21757351
      supporting_text: required for sorting EGFR to the MVB
    - &id023
      reference_id: PMID:21757351
      supporting_text: endosomal ubiquitin homeostasis
    - &id024
      reference_id: PMID:22405001
      supporting_text: essential for degradation of antiviral cell-surface proteins
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation.
    action: ACCEPT
    reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: endosome localization is supported and relevant to UBAP1/ESCRT-I function.
    action: ACCEPT
    reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
    additional_reference_ids: &id019
    - PMID:21757351
    - file:human/UBAP1/UBAP1-uniprot.txt
    - file:human/UBAP1/UBAP1-notes.md
    supported_by: &id020
    - &id025
      reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: Endosome
    - &id026
      reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: Predominantly cytosolic
    - &id027
      reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: Recruited to endosomes as part of the ESCRT-I complex
    - &id028
      reference_id: PMID:21757351
      supporting_text: endosome-specific ESCRT-I complex
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: cytosol is supported as a localization context but is not the core functional site.
    action: KEEP_AS_NON_CORE
    reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal
      ESCRT-I cargo sorting.
    additional_reference_ids: &id017
    - PMID:21757351
    - file:human/UBAP1/UBAP1-uniprot.txt
    - file:human/UBAP1/UBAP1-notes.md
    supported_by: &id018
    - reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: Predominantly cytosolic
    - reference_id: file:human/UBAP1/UBAP1-uniprot.txt
      supporting_text: Cytoplasm, cytosol
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Ubiquitin binding is a core UBAP1 molecular-function annotation.
    action: ACCEPT
    reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core
      UBAP1/ESCRT-I endosomal cargo-sorting process.
    action: ACCEPT
    reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent UBAP1 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative molecular function is ubiquitin binding, and the informative component/process terms are ESCRT-I
      complex and MVB sorting.
    proposed_replacement_terms:
    - id: GO:0043130
      label: ubiquitin binding
    - id: GO:0000813
      label: ESCRT I complex
    additional_reference_ids:
    - PMID:21757351
    - PMID:22405001
    - file:human/UBAP1/UBAP1-uniprot.txt
    - file:human/UBAP1/UBAP1-notes.md
    - PMID:21757351
    - PMID:22405001
    - file:human/UBAP1/UBAP1-uniprot.txt
    - file:human/UBAP1/UBAP1-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: cytosol is supported as a localization context but is not the core functional site.
    action: KEEP_AS_NON_CORE
    reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal
      ESCRT-I cargo sorting.
    additional_reference_ids: *id017
    supported_by: *id018
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IPI
  original_reference_id: PMID:21757351
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation.
    action: ACCEPT
    reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
    action: ACCEPT
    reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
    additional_reference_ids: *id019
    supported_by: *id020
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: multivesicular body assembly is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process.
    action: ACCEPT
    reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0043328
    label: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body
      sorting pathway
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular
      body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process.
    action: ACCEPT
    reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0090148
    label: membrane fission
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: Membrane fission is over-transferred for UBAP1 as written.
    action: MARK_AS_OVER_ANNOTATED
    reason: The cited structural/autophagy work uses a VPS37B-MVB12A-containing ESCRT-I headpiece and VPS28 mutants, not UBAP1-containing
      ESCRT-I.
    proposed_replacement_terms:
    - id: GO:0000813
      label: ESCRT I complex
    - id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
    additional_reference_ids:
    - PMID:32424346
    - file:human/UBAP1/UBAP1-notes.md
    - PMID:21757351
    - PMID:22405001
    - file:human/UBAP1/UBAP1-uniprot.txt
    - file:human/UBAP1/UBAP1-notes.md
    supported_by:
    - reference_id: PMID:32424346
      supporting_text: comprising TSG101-VPS28-VPS37B-MVB12A
    - reference_id: PMID:32424346
      supporting_text: Mutation of VPS28 helical interface residues
    - *id007
    - *id008
- term:
    id: GO:0005768
    label: endosome
  evidence_type: EXP
  original_reference_id: PMID:21757351
  qualifier: located_in
  review:
    summary: endosome localization is supported and relevant to UBAP1/ESCRT-I function.
    action: ACCEPT
    reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
    additional_reference_ids: *id019
    supported_by: *id020
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-184269
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
    action: ACCEPT
    reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
    additional_reference_ids: *id019
    supported_by: *id020
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3149434
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
    action: ACCEPT
    reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
    additional_reference_ids: *id019
    supported_by: *id020
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3159232
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
    action: ACCEPT
    reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
    additional_reference_ids: *id019
    supported_by: *id020
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917696
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
    action: ACCEPT
    reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
    additional_reference_ids: *id019
    supported_by: *id020
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917730
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to UBAP1/ESCRT-I function.
    action: ACCEPT
    reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex.
    additional_reference_ids: *id019
    supported_by: *id020
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:21757351
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation.
    action: ACCEPT
    reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:21757351
  qualifier: located_in
  review:
    summary: cytosol is supported as a localization context but is not the core functional site.
    action: KEEP_AS_NON_CORE
    reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal
      ESCRT-I cargo sorting.
    additional_reference_ids: *id017
    supported_by: *id018
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IDA
  original_reference_id: PMID:21757351
  qualifier: enables
  review:
    summary: Ubiquitin binding is a core UBAP1 molecular-function annotation.
    action: ACCEPT
    reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IMP
  original_reference_id: PMID:21757351
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core
      UBAP1/ESCRT-I endosomal cargo-sorting process.
    action: ACCEPT
    reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000054
  qualifier: located_in
  review:
    summary: cytoplasm is supported as a localization context but is not the core functional site.
    action: KEEP_AS_NON_CORE
    reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal
      ESCRT-I cargo sorting.
    additional_reference_ids: *id017
    supported_by: *id018
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative
    changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000054
  title: Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living
    cells
  findings: []
- id: PMID:21757351
  title: UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:32424346
  title: A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.
  findings: []
- id: Reactome:R-HSA-184269
  title: Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by the ESCRT-I complex
  findings: []
- id: Reactome:R-HSA-3149434
  title: Transport of GAG to the Plasma Membrane
  findings: []
- id: Reactome:R-HSA-3159232
  title: Recruitment Of HIV Virion Budding Machinery
  findings: []
- id: Reactome:R-HSA-917696
  title: Cargo Sequestration
  findings: []
- id: Reactome:R-HSA-917730
  title: Cargo Recognition And Sorting
  findings: []
- id: PMID:22405001
  title: The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain.
  findings: []
- id: file:human/UBAP1/UBAP1-uniprot.txt
  title: UniProtKB record for human UBAP1
  findings: []
- id: file:human/UBAP1/UBAP1-notes.md
  title: UBAP1 review notes
  findings: []
core_functions:
- description: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant that organizes a TSG101-VPS28-VPS37A-UBAP1 complex
    for ubiquitinated cargo sorting.
  molecular_function:
    id: GO:0043130
    label: ubiquitin binding
  directly_involved_in:
  - id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  - id: GO:0036258
    label: multivesicular body assembly
  locations:
  - id: GO:0005768
    label: endosome
  - id: GO:0010008
    label: endosome membrane
  in_complex:
    id: GO:0000813
    label: ESCRT I complex
  supported_by:
  - *id012
  - *id013
  - *id014
  - *id015
  - *id016
  - *id007
  - *id008
  - *id009
  - *id010
  - *id011
  - *id021
  - *id022
  - *id023
  - *id024
  - *id025
  - *id026
  - *id027
  - *id028
proposed_new_terms: []
suggested_questions:
- question: Should UBAP1 membrane-fission annotations be removed or kept non-core unless UBAP1-containing ESCRT-I is directly
    tested in membrane-scission/autophagosome-closure assays?
  experts:
  - GO ESCRT curators
  - GO autophagy editors
- question: Should generic UBAP1 protein-binding annotations be replaced by ubiquitin binding and ESCRT-I complex membership?
  experts:
  - GO molecular function editors
  - UniProt curators
suggested_experiments:
- experiment_type: UBAP1-containing ESCRT-I membrane remodeling assay
  hypothesis: UBAP1-containing ESCRT-I specializes in endosomal ubiquitinated cargo sorting and should not be assumed to provide
    the same membrane-fission function as MVB12A-containing ESCRT-I without direct evidence.
  description: Compare purified or reconstituted UBAP1-ESCRT-I and MVB12A-ESCRT-I complexes in membrane-remodeling assays
    and in cell-based autophagosome-closure assays.
- experiment_type: UBAP1 ubiquitin-binding rescue
  hypothesis: UBAP1 SOUBA/UBA-mediated ubiquitin binding is required for endosomal cargo sorting.
  description: Rescue UBAP1 knockout cells with wild-type and SOUBA/UBA mutants and measure EGFR/BST2 cargo degradation, endosomal
    ubiquitin homeostasis, and ESCRT-I recruitment.